Engineering Genetic Circuits I use the book and slides of Chris J. Myers Lecture 0: Preface Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 1 / 19
Samuel Florman Engineering is the art or science of making practical. Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 2 / 19
Robert Heinlein One man’s “magic” is another man’s engineering. Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 3 / 19
Bioinformatics Biology is now both a lab-based science and an information science. Biologists have had to draw assistance from those in mathematics, computer science, and engineering. Result was development of bioinformatics and computational biology . Major goal is to extract new biological insights from large and noisy sets of data generated by high throughput technologies. Must create and maintain databases with massive amounts of data. Must be able to efficiently access, submit, and revise this data. Latest software must even analyze and interpret this data. In this course, we use the term bioinformatics to refer to the analysis of static data such as sequence analysis of DNA and protein sequences, techniques for finding genes or evolutionary patterns, and cluster analysis of microarray data. Bioinformatics algorithms are not covered in this course. Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 4 / 19
Systems Biology The focus of this course is the modeling, analysis, and design methods for systems biology . Systems biology is the study of the mechanisms underlying complex molecular processes as integrated into systems or pathways made up of many interacting genes and proteins. Concerned with the analysis of dynamic models. Made possible by new experimental methods such as: cDNA microarrays and oligonucleotide chips. Mass spectrometric identification of gel-separated protiens. 2-hybrid systems. Genome-wide location analysis (ChIP-to-chip) Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 5 / 19
Systems Biology (cont) Systems biology involves: Collection of large experimental data sets, Constructing mathematical models from this data, Designing software to accurately and efficiently analyze these models in silico (i.e., on a computer), Comparing numerical simulations with the experimental data, and Designing new synthetic biological systems. Ultimate goal is to develop methods which can give reasonable predictions of experimental results. While it will never replace experimental methods, may help experimentalists make better use of their time. Also may gain insight into mechanisms used by these biological processes which may not be obtained by experiments. Eventually, may be possible that they could have substantial impact on our society such as aiding in drug discovery. Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 6 / 19
Biological Networks Metabolic networks are enzymatic processes that transform food into energy, and perform both biosynthesis and biodegradation. Protein networks are communication and signaling networks which are composed of basic reactions between two or more proteins. Genetic regulatory networks , or genetic circuits , regulate gene expression at many molecular levels. The focus of this course are methods for modeling, analysis, and design of genetic circuits. Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 7 / 19
Standard Data Formats: SBML Standards for sequence data were absolutely essential. For systems biology, standard data formats are being developed. One is the systems biology markup language (SBML). XML-based language to represent chemical reaction networks. All networks described in this lecture can be reduced to a set of bio-chemical reactions. SBML model consists of a list of the species and their reactions. A reaction includes a list of reactants, products, and modifiers. Also includes a mathematical description of the kinetic rate law governing the dynamics of this reaction. SBML is ugly, but GUIs have been developed. Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 8 / 19
Biological Databases Another essential item in the genomic-age was the development of biological databases . These provide repositories for storing large bodies of data that can be easily updated, queried, and retrieved. Databases store many things ranging from nucleotide sequences within GenBank to biomedical literature at PubMed. Recently, a database for SBML models has been started. Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 9 / 19
Tools Last essential piece is tools. Excellent list of bioinformatics tools at the NCBI website. List of systems biology tools that support SBML can be found at at the SBML website. The remainder of this course concentrates on describing the methods used by tools being developed for systems and synthetic biology. Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 10 / 19
Engineering Methods Engineers have experience in modeling and analyzing systems. Can take a circuit view of a genetic circuit (Science1995). Collaborations needed between engineers and biologists. Goal of this course is to facilitate these collaborations. Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 11 / 19
� � � � � � � � � � � � � � � � � � � � The Engineering Approach Insert into Genetic Circuit Plasmid Host Set of Perform Construct Experiments Experiments Plasmid Biological Experimental DNA Knowledge Sequence Data � �������� � SBML Model TechMap Library Learn Model Logic Abstraction/ Models Equations Simulation Construct Simulation � Synthesis HDL Experiments Data Modeling Analysis Design Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 12 / 19
� � � � � � � � � � � � � � � � � � � � Chapter 1: An Engineer’s Guide to Genetic Circuits Insert into Genetic Circuit Plasmid Host Set of Perform Construct Experiments Experiments Plasmid Biological Experimental DNA Knowledge Sequence Data � �������� � SBML Model TechMap Library Learn Model Logic Abstraction/ Models Equations Simulation Construct Simulation � Synthesis HDL Experiments Data Modeling Analysis Design Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 13 / 19
� � � � � � � � � � � � � � � � � � � � Chapter 2: Learning Models Insert into Genetic Circuit Plasmid Host Set of Perform Construct Experiments Experiments Plasmid Biological Experimental DNA Knowledge Sequence Data � �������� � SBML Model TechMap Library Learn Model Logic Abstraction/ Models Equations Simulation Construct Simulation � Synthesis HDL Experiments Data Modeling Analysis Design Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 14 / 19
� � � � � � � � � � � � � � � � � � � � Chapter 3: Differential Equation Analysis Insert into Plasmid Genetic Circuit Host Set of Perform Construct Experiments Experiments Plasmid Biological Experimental DNA Knowledge Sequence Data � �������� � SBML Model TechMap Library Learn Model Logic Abstraction/ Models Equations Simulation Construct Simulation � Synthesis HDL Experiments Data Modeling Analysis Design Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 15 / 19
� � � � � � � � � � � � � � � � � � � � Chapter 4: Stochastic Analysis Insert into Plasmid Genetic Circuit Host Set of Perform Construct Experiments Experiments Plasmid Biological Experimental DNA Knowledge Sequence Data � �������� � SBML Model TechMap Library Learn Model Logic Abstraction/ Models Equations Simulation Construct Simulation � Synthesis HDL Experiments Data Modeling Analysis Design Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 16 / 19
� � � � � � � � � � � � � � � � � � � � Chapter 5: Reaction-Based Abstraction Insert into Plasmid Genetic Circuit Host Set of Perform Construct Experiments Experiments Plasmid Biological Experimental DNA Knowledge Sequence Data � �������� � SBML Model TechMap Library Learn Model Logic Abstraction/ Models Equations Simulation Construct Simulation � Synthesis HDL Experiments Data Modeling Analysis Design Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 17 / 19
� � � � � � � � � � � � � � � � � � � � Chapter 6: Logical Abstraction Insert into Genetic Circuit Plasmid Host Set of Perform Construct Experiments Experiments Plasmid Biological Experimental DNA Knowledge Sequence Data � �������� � SBML Model TechMap Library Learn Model Logic Abstraction/ Models Equations Simulation Construct Simulation � Synthesis HDL Experiments Data Modeling Analysis Design Chris J. Myers (Lecture 0: Preface) Engineering Genetic Circuits 18 / 19
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